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研究生:葉齡文
研究生(外文):Yeh, Lin-Wen
論文名稱:UTX/KDM6A藉由控制DNA複製及修復路徑以維持腫瘤的生長
論文名稱(外文):UTX/KDM6A contributes to tumor maintenance by controlling DNA replication and repair pathways
指導教授:王書品
指導教授(外文):Wang, Shu-Ping
口試委員:周玉山譚婉玉謝小燕陳昇宏
口試委員(外文):Jou, Yuh-ShanTarn, Woan-YuhShieh, Sheau-YannChen, Sheng-hong
口試日期:2024-07-02
學位類別:博士
校院名稱:國立陽明交通大學
系所名稱:分子醫學博士學位學程
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2024
畢業學年度:112
語文別:英文
論文頁數:89
中文關鍵詞:UTX組蛋白去甲基酶ATRPARP1聚腺苷酸二磷酸核糖轉移酶DNA複製DNA修補
外文關鍵詞:UTXPARP1DNA replicationDNA repair
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中文摘要 ........................................................................................................................................................i
Abstract .................................................................................................................................ii
Table of contents ...................................................................................................................iii
List of figure .........................................................................................................................v
List of table ..........................................................................................................................vi
Introduction ..........................................................................................................................1
1-1 Histone methylation ......................................................................................................................1
1-1-1 The writer of H3K27 methylation .......................................................................2
1-1-2 The eraser of H3K27 methylation .......................................................................3
1-1-3 The role of H3K27 methylation in cancer ...........................................................4
1-2 DNA replication ...............................................................................................................................6
1-2-1 The mechanism of DNA replication ...................................................................6
1-2-2 Replication stress ................................................................................................7
1-2-3 Replication stress and cancer therapy .................................................................9
1-3 DNA damage ....................................................................................................................................10
1-3-1 DNA damage response ........................................................................................11
1-3-2 DNA repair and cancer therapy ...........................................................................12
Materials and methods ..........................................................................................................14
2-1 Cell culture ........................................................................................................................................14
2-2 Clonogenic survival assay ...........................................................................................................14
2-3 Western blot analysis ...................................................................................................................14
2-4 Cell viability assay ........................................................................................................................15
2-5 Quantitive real-time PCR .............................................................................................................15
2-6 Chromatin immunoprecipitation assay ...................................................................................15
2-7 Flow cytometry analysis .............................................................................................................16
2-8 Bromodeoxyuridine incorporation assay ...............................................................................17
2-9 Immunofluorescence assay .........................................................................................................17
2-10 Homologous recombination activity analysis ....................................................................18
2-11 Fluorescence recovery after photobleaching (FRAP) ......................................................18
2-12 Apoptosis analysis ......................................................................................................................19
2-13 Domain mapping ..........................................................................................................................19
2-14 Immunoprecipitation ...................................................................................................................20
2-15 In vivo mouse xenograft ...........................................................................................................20
Results ..................................................................................................................................21
Conclusion and discussion ....................................................................................................32
Future direction .....................................................................................................................36
Figure ....................................................................................................................................38
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